First Online: 01 November 2012Received: 13 June 2012Accepted: 11 October 2012

Abstract

BackgroundIn addition to stimulating linear growth in children, growth hormone GH influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis : There are different dose-dependent thresholds for metabolic effects in response to GH treatment.

MethodA randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens a individualized GH dose including six different dose groups ranging from 17–100 μg-kg-day n=87 and b fixed GH dose of 43 μg-kg-day n=41. The individualized GH dose group was used for finding dose–response effects, where the effective GH dose ED 50% required to achieve 50% Δ effect was calculated with piecewise linear regressions.

ResultsDifferent thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect ED 50%, with 90% confidence interval was calculated as 33±24.4 μg-kg-day for Δ left ventricular diastolic diameter cm, 39±24.5 μg-kg-day for Δ alkaline phosphatase μkat-L, 47±43.5 μg-kg-day for Δ lean soft tissue SDS, 48±35.7 μg-kg-day for Δ insulin mU-L, 51±47.6 μg-kg-day for Δ height SDS, and 57±52.7 μg-kg-day for Δ insulin-like growth factor I IGF-I SDS. Even though lipolysis was seen in all subjects, there was no dose–response effect for Δ fat mass SDS or Δ leptin ng-ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial.

ConclusionsDose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.